Academic Journal
Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity
| العنوان: | Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity |
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| المؤلفون: | Mobbs, Jesse I., Belousoff, Matthew J., Harikumar, Kaleeckal G., Piper, Sarah J., Xu, Xiaomeng, Furness, Sebastian G. B., Venugopal, Hari, Christopoulos, Arthur, Danev, Radostin, Wootten, Denise, Thal, David M., Miller, Laurence J., Sexton, Patrick M. |
| المساهمون: | Walters, Kylie J., Australian Research Council, National Health and Medical Research Council, Takeda Science Foundation, Japan Science and Technology Agency PRESTO Grant |
| المصدر: | PLOS Biology ; volume 19, issue 6, page e3001295 ; ISSN 1545-7885 |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2021 |
| المجموعة: | PLOS Publications (via CrossRef) |
| الوصف: | G protein–coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11–GPCR complexes, the Gq–α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from “unwinding” of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1371/journal.pbio.3001295 |
| الاتاحة: | http://dx.doi.org/10.1371/journal.pbio.3001295 https://dx.plos.org/10.1371/journal.pbio.3001295 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.D5062D94 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pbio.3001295 |
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